Microfluidic peristaltic pump, method and pumping system

ABSTRACT

A microfluidic peristaltic pump has an inflow channel, a first pumping chamber, which is operatively connected to the inflow channel by a first channel, and a first membrane. The pump also has a second pumping chamber, which is operatively connected to the inflow channel by a second channel, and a second membrane. A fluidic resistance of the first channel is different from a fluidic resistance of the second channel, and each channel is configured to realize a throttling function, such that the first and second membranes are deflected in a time sequence when a pressure is applied in the inflow channel, to realize a pumping function.

This application claims priority under 35 U.S.C. §119 to patent application no. DE 10 2012 220 403.2, filed on Nov. 9, 2012 in Germany, the disclosure of which is incorporated herein by reference in its entirety.

BACKGROUND

For processing microfluidic sequences in miniaturized diagnostic systems (Labs-on-a-Chip, LOCs), among the devices integrated on the LOC are micro pumps. Apart from avoiding contamination of external pumps with specimen liquids, this provides the advantage in particular that even very small amounts of specimen and low pumping rates can be inexpensively realized.

Already generally known from the prior art as examples of different types of configuration are electroosmotic pumps, membrane pumps combined with valves, micromechanical peristaltic pumps, electrically actuated peristaltic pumps and thermo-pneumatically actuated peristaltic pumps.

U.S. Pat. No. 7,217,367 B2 describes a system for microfluidic chromatography, in which a microfluidic peristaltic pump is used. The individual pumping chambers of the pump are respectively activated by way of an associated valve, with the result that the production expenditure is correspondingly increased.

SUMMARY

The microfluidic peristaltic pumps and the pumping system defined herein have the advantage over conventional solutions that, as a result of the effect of the individual channels as throttles in the (pneumatic) path to the pumping chambers, just a single integrated valve or just a single interface with the outside world is now necessary for all the pumping chambers, while in the case of conventional pneumatic peristaltic pumps each pumping chamber has to be individually actuated with the aid of an associated valve. On account of this simplification of the structural configuration of the pump according to the disclosure, both lower costs for the LOCs and the external activation unit and increased reliability are obtained. The use of a layered structure comprising polymer substrates and a polymer membrane makes possible a particularly low-cost way of realizing extremely small structures, which are necessary for the throttling of gases.

By contrast with known pumps, the number of pumping chambers can be increased at will, without additional interfaces with the outside or additional valves becoming necessary.

By contrast with known pumps, it is possible by skillful configuration of the pumping chambers and the integrated throttles to specifically activate or deactivate more than just one single pump by way of the switching frequency of the controlling valve. For example, in this case one pump has a low-pass characteristic and is activated at low switching frequencies, and a further pump has a high-pass characteristic and is activated at high switching frequencies. In this case, just a single valve or a single interface with the outside world is necessary, even in the case of multiple pumps.

An (inflow) channel is intended to be understood as meaning a structure that realizes a tubular connection, and may be formed for example as a (microfluidic) flow channel in a layered structure or as a separate line, for example in the manner of a hose or a small tube.

According to a further configuration of the microfluidic peristaltic pump according to the disclosure, the fluidic resistance of a channel of a constant cross section is determined substantially by its length. Consequently, the channel acts like a (pneumatic) throttle that is integrated in the channel, whereby the deflection of the membrane of a pumping chamber into defined cavities can be controlled in terms of time by the integrated throttles.

According to a further configuration of the microfluidic peristaltic pump according to the disclosure, the first membrane and the second membrane are formed by a polymer membrane. Here, only a single polymer membrane is used, the individual membranes of the respective pumping chambers being realized by a local deflection of this polymer membrane. In this way, the two membranes may be formed as an integral component. The polymer membrane may for example be formed from an elastomer, a thermoplastic elastomer, thermoplastics or a film of hotmelt adhesive. The thickness of the polymer membrane may be between 5 μm and 300 μm.

According to a further configuration of the microfluidic peristaltic pump according to the disclosure, the first membrane and the second membrane may be deflected into a flow channel, which is formed in a first polymer substrate. As described above, the use of a polymeric layered structure in conjunction with a polymer membrane for the individual membranes of the pumping chambers offers significant advantages with regard to their low-cost production for the realization of the microfluidic peristaltic pump according to the disclosure. The polymer substrate may be formed from thermoplastics, such as for example PC, PP, PE, PMMA, COP or COC. The thickness of the polymer substrate may be between 0.5 mm and 5 mm The diameter of the channels for the connection to the pumping chamber in a polymer substrate may be between 200 μm and 3 mm.

According to a further configuration of the microfluidic peristaltic pump according to the disclosure, the pumping chambers may be formed as expansions. The expansions may in this case extend for example into the polymer substrate. Here, the cross section of the pumping chambers may be variable on account of an expansion along one direction. The volume of a pumping chamber may be between 1 mm³ and 1000 mm³.

According to a further configuration of the microfluidic peristaltic pump according to the disclosure, the first pumping chamber may have substantially the same cross section as an inflow connected to the first pumping chamber, and the second pumping chamber may have substantially the same cross section as an outflow connected to the second pumping chamber. This allows the production of the pumping chambers and the associated inflows and outflows to be simplified in an advantageous way. The microfluidic peristaltic pump according to the disclosure may transport and move a fluid both in the direction from the inflow to the outflow and, with corresponding activation of the pumping chambers, in the direction from the outflow to the inflow.

According to a further configuration of the microfluidic peristaltic pump according to the disclosure, the first channel and the second channel may be formed in the polymer membrane. The channels are formed here by recesses in the polymer membrane, with the result that the height of the channels is defined by the thickness of the polymer membrane, whereby very shallow channels can be realized. The diameter of the channels in the polymer membrane may be between 1 μm and 100 μm.

According to a further configuration of the microfluidic peristaltic pump according to the disclosure, the first channel and the second channel may be formed in a second polymer membrane. Preferably, the two polymer membranes are formed separately and are arranged at a distance from one another on different planes. This has the advantage in particular that a different polymer membrane can be used for the channels than the polymer membrane that is responsible for the deflection of the pumping chambers. Thus, the polymer membrane for the channels may for example be chosen to be particularly thin (high fluidic resistance for the throttling channels) and the polymer membrane for the pumping chambers may be chosen to be thicker (improved reliability during pumping). In addition, the pumping unit with the channels may be produced on a much smaller base area, since the channels can also run over the pumping chambers.

According to a further configuration of the microfluidic peristaltic pump according to the disclosure, the channels may be operatively connected to the pumping chambers by way of through-holes. In the case of this configuration, together with the separation described above of the polymer membranes for the channels and the pumping chambers, advantages in the production of the structures for the connection of channels and pumping chambers are obtained, since they can be realized with the aid of through-holes.

According to a further configuration of the microfluidic peristaltic pump according to the disclosure, the inflow channel may be formed in a third polymer substrate, which is arranged above the second polymer membrane. Here, a stable and reliable connection of the inflow channel is provided in particular when there are separate polymer membranes of the channels and of the pumping chambers.

Also described herein is a pumping system, having a first microfluidic peristaltic pump and a second microfluidic pump, the first pump and the second pump being connected to the inflow channel, and the respective products of the fluidic resistance of a channel and the fluidic capacity of the associated pumping chamber differing from one another for the first pump and the second pump, one pump having a low-pass characteristic and another pump having a high-pass characteristic. In this case, the following relationship applies: R_(ij)·C_(ij)≠R_(i+1j+j)·C_(i+1j+j). The index i in this case describes the respective pump of the pumping system and the index j describes the respective pumping chamber within the associated pump i. Thus, for example, a first pump has a low-pass characteristic and is activated at (a) low actuation frequency (frequencies), and a second pump has a high-pass characteristic and is activated at (a) high actuation frequency (frequencies).

Also described herein is a method for operating a microfluidic peristaltic pump which has an inflow, a first pumping chamber, which is operatively connected to the inflow channel by way of a first channel, and a first membrane, a second pumping chamber, which is operatively connected to the inflow channel by way of a second channel, and a second membrane, the fluidic resistance of the first channel being different from the fluidic resistance of the second channel, comprising the steps of realizing a throttling function by each channel, with the result that the respective membranes are deflected in a time sequence when a pressure is applied in the inflow channel, to realize a pumping function.

The disclosed method has the advantage that, as a result of the effect of the individual channels as throttles in the (pneumatic) path to the pumping chambers, now just a single integrated valve or just a single interface with the outside world is necessary for all the pumping chambers, while in the case of conventional pneumatic peristaltic pumps each pumping chamber must be actuated individually with the aid of an associated valve. On account of this simplification of the operating mode of the associated pump according to the disclosure, lower costs, both for the LOCs and the external activation unit, and increased reliability are obtained.

The required structures in the polymer substrates and membranes may be produced for example by milling, injection molding, hot stamping, punching or laser structuring.

BRIEF DESCRIPTION OF THE DRAWINGS

The present disclosure is explained on the basis of the accompanying drawings, in which:

FIG. 1 shows a schematic view of a microfluidic peristaltic pump according to the disclosure,

FIG. 2 shows a plan view of a microfluidic peristaltic pump according to a first embodiment of the present disclosure,

FIG. 3 shows a sectional view of the microfluidic peristaltic pump from FIG. 2 along the line A-A,

FIG. 4 shows a sectional view of the microfluidic peristaltic pump from FIG. 2 along the line B-B,

FIG. 5 shows a plan view of a microfluidic peristaltic pump according to the second embodiment of the present disclosure, and

FIG. 6 shows a sectional view of the microfluidic peristaltic pump from FIG. 5 along the line C-C.

DETAILED DESCRIPTION

FIG. 1 shows a schematic view of a microfluidic peristaltic pump 100 according to the disclosure in conjunction with the sequence of a pumping operation of the pump 100 according to the disclosure.

The microfluidic peristaltic pump 100 according to the disclosure is supplied with compressed air for actuating the n pumping chambers 20, 50, 51, 52 and atmospheric pressure or a vacuum by way of two pneumatic inlets 5 and 8. The pneumatic inlets 5 and 8 are respectively separated by a first valve 1 and a second valve 2 from an inflow channel 10, which divides into n channels 30, 60, 61, 62. The inflow channel 10 and the channels 30, 60, 61, 62 may be formed independently of one another as a microfluidic flow channel in a layered structure or as a separate line, for example in the manner of a hose or small tube. Each channel 30, 60, 61, 62 has a specific fluidic resistance R₁ to R_(n), where

R₁<R₂< . . . <R_(i)< . . . <R_(n) for i=1 . . . n.

The channels 30, 60, 61, 62 are connected to the n pumping chambers 20, 50, 51, 52, which are separated from the supplying channels by a flexible membrane 40, for example a polymer membrane. The pumping chambers 20, 50, 51, 52 are fluidically connected to one another. Also connected to the first pumping chamber 20 is a fluidic inflow 200 and also connected to the nth pumping chamber 52 is an outflow 300. The pumping chambers 20, 50, 51, 52 are configured as expansions.

As an alternative to this, the pumping chambers 20, 50, 51, 52 may have the same cross section as the inflow 200 or as the outflow 300.

The valves 1 and 2 are switched such that either the pneumatic inflow 5 or 8 is connected to the fluidic network downstream thereof (instead of two valves 1 and 2, a single changeover valve may also be used). If a positive pressure is connected to the inflow 1 and the inflow 8 is connected to atmosphere, and the positive pressure is transferred to the fluidic network, the different fluidic resistances R_(i) in the channels 30, 60, 61, 62 have the effect that the flexible polymer membrane 40 in the pumping chambers 20, 50, 51, 52 is deflected with a time delay and the fluid is pumped in the direction of the outflow 300, until the last pumping chamber 52 has been fully deflected. The channels 30, 60, 61 and 62 with the fluidic resistances R_(i) accordingly act as pneumatic throttles, it being possible for a different actuation medium to be used instead of air, for example a mineral oil.

If the valves 1 and 2 are subsequently switched over, the restoring forces of the polymer membranes 40 in the respective pumping chambers 20, 50, 51, 52 in conjunction with the different fluidic resistances R_(i) thereto have the effect that the polymer membranes 40 relax in the reverse sequence, with the result that the fluid displaced in the direction of the outflow 300 cannot flow back and new fluid is sucked in from the direction of the inflow 200. The next cycle can then be started by switching over of the valves 1, 2.

In another embodiment (not represented), the connection 8 is not at atmospheric pressure, but negative pressure, in order to allow the withdrawal of the polymer membranes 40, 70 to be carried out more quickly and more reliably.

FIG. 2 shows a plan view of a microfluidic peristaltic pump 100 according to a first embodiment of the present disclosure. FIG. 3 shows a sectional view of the microfluidic peristaltic pump from FIG. 2 along the line A-A, and FIG. 4 shows a sectional view of the microfluidic peristaltic pump from FIG. 2 along the line B-B. With reference to FIGS. 2 to 4, the first embodiment of the microfluidic peristaltic pump according to the disclosure will now be described. This embodiment and the embodiment described thereafter preferably have lateral dimensions of 10×10 mm² to 200×200 mm² of the pump.

The microfluidic peristaltic pump 100 consists of a three-layer structure comprising a first polymer substrate 80 and a second polymer substrate 90, which are separated from one another by a flexible polymer membrane 110. The first polymer substrate 80 has a pneumatic inlet 5, which is connected to three channels 30, 60, 61 by way of an inflow channel 10. The channels 30, 60, 61 are formed by recesses in the polymer membrane 110, with the result that the height of the channels 30, 60, 61 is defined by the thickness of the polymer membrane 110, whereby very shallow channels can be realized. In this exemplary embodiment, the fluidic resistance of the channels 30, 60, 61 is defined by their differing length.

The channels 30, 60, 61 end in connection channels 31, 32, 33 in the second polymer substrate 90. The pumping chambers 20, 50, 51 respectively have a membrane 40, 70, 71, which separates the pumping chamber from a flow channel 150 in the first polymer substrate 80 into which the deflected membrane 40, 70, 71 extends. A positive pressure leads through the mechanism to a time-delayed deflection of the membranes 40, 70, 71 underneath the connection channels 31, 32, 33. For this purpose, the membranes 40, 70, 71 are not connected to the second polymer substrate 90 in the direct vicinity of the connection channels 31, 32, 33. In the region between the connection channels 31, 32, 33, however, the polymer membrane is connected to the second polymer substrate 90 in such a way that the displacement units of the pump 100 are pneumatically isolated. The membranes 40, 70, 71 are formed integrally with one another to form the polymer membrane 110, and form a single component.

In a further embodiment (not represented), the fluidic resistances R_(i) are not realized as a parallel connection but as a series connection, i.e. the pumping chambers are connected one behind the other by the channels with fluidic resistances

FIG. 5 shows a plan view of a microfluidic peristaltic pump 100 according to a second embodiment of the present disclosure, and FIG. 6 shows a sectional view of the microfluidic peristaltic pump 100 from FIG. 5 along the line C-C. With reference to FIGS. 5 and 6, the second embodiment of the microfluidic peristaltic pump according to the disclosure will now be described.

By contrast with the first embodiment, the second embodiment has an additional polymer membrane 120 and an additional polymer substrate 130. The additional polymer substrate 130 has a pneumatic inlet 5. The channels 30, 60, 61 are not located in the polymer membrane 110, but are formed in the second polymer membrane 120, and consequently in a different plane. The fluidic connection to the pumping chambers 20, 50 takes place by way of through-holes 140, 141, 142 in the second polymer substrate 90. This embodiment has the advantage in particular that a different polymer membrane 120 can be used for the channels 30, 60, 61 than the polymer membrane 110 that is responsible for the deflection of the pumping chambers 20, 50. Thus, the second polymer membrane 120 may for example be chosen to be particularly thin (high fluidic resistance for the channels 30, 60, 61) and the polymer membrane 110 may be chosen to be thicker (improved reliability during pumping). In addition, the pumping unit including the channels 30, 60, 61 may be produced on a much smaller base area, since the channels 30, 60, 61 can also run over the pumping chambers.

The pumping chambers 20, 50 may be treated as fluidic capacities C_(i). In a further embodiment (not represented), a first pump may be configured such that the product of the capacities C_(i) and the resistances R_(i) is great. A second pump is configured such that R_(i)*C_(i) is small. In this way, long reaction times for the first pump and short reaction times for the second pump are obtained. This leads in an advantageous way to only the second pump operating for fast switching frequencies of valves, but both pumps operating in the case of slower switching frequencies. In this way it is possible with just a single pneumatic interface to activate the pump selectively and to extend the possibilities for realizing microfluidic sequences. 

What is claimed is:
 1. A microfluidic peristaltic pump, comprising: an inflow channel; a first pumping chamber operatively connected to the inflow channel by a first channel; a first membrane; a second pumping chamber operatively connected to the inflow channel by a second channel; and a second membrane, wherein a fluidic resistance of the first channel is different from a fluidic resistance of the second channel and each channel is configured to produce a throttling function such that the first and second membranes are deflected in a time sequence when a pressure is applied in the inflow channel, to produce a pumping function.
 2. The microfluidic peristaltic pump according to claim 1, wherein at least one of the first and second channels is configured with a constant cross section such that the fluidic resistance of the at least one of the first and second channels is determined substantially by its length.
 3. The microfluidic peristaltic pump according to claim 1, wherein the first membrane and the second membrane are formed by a polymer membrane.
 4. The microfluidic peristaltic pump according to claim 1, wherein the first membrane and the second membrane are configured to be deflected into a flow channel formed in a first polymer substrate.
 5. The microfluidic peristaltic pump according to claim 1, wherein the first and second pumping chambers are formed as expansions.
 6. The microfluidic peristaltic pump according to claim 1, wherein: a cross section of the first pumping chamber is substantially the same as a cross section of an inflow connected to the first pumping chamber, and a cross section of the second pumping chamber is substantially the same as a cross section of an outflow connected to the second pumping chamber.
 7. The microfluidic peristaltic pump according to claim 3, wherein the first channel and the second channel are formed in the polymer membrane.
 8. The microfluidic peristaltic pump according to claim 1, wherein the first channel and the second channel are formed in a second polymer membrane.
 9. The microfluidic peristaltic pump according to claim 8, wherein the first channel, the second channel, and a third channel are operatively connected to the first pumping chamber, the second pumping chamber, and a third pumping chamber by through-holes.
 10. The microfluidic peristaltic pump according to claim 8, wherein the inflow channel is formed in a third polymer substrate arranged above the second polymer membrane.
 11. A pumping system, comprising: an inflow channel; a first microfluidic peristaltic pump, including: a first pumping chamber operatively connected to the inflow channel by a first channel, a first membrane, a second pumping chamber operatively connected to the inflow channel by a second channel, and a second membrane, wherein a fluidic resistance of the first channel is different from a fluidic resistance of the second channel and each channel is configured to produce a throttling function such that the first and second membranes are deflected in a time sequence when a pressure is applied in the inflow channel, to produce a pumping function; and a second microfluidic pump, including: a third pumping chamber operatively connected to the inflow channel by a third channel, a third membrane, a fourth pumping chamber operatively connected to the inflow channel by a fourth channel, and a fourth membrane, wherein a fluidic resistance of the third channel is different from a fluidic resistance of the fourth channel and each channel is configured to produce a throttling function such that the third and fourth membranes are deflected in a time sequence when a pressure is applied in the inflow channel, to produce a pumping function, wherein the first pump and the second pump are connected to the inflow channel, wherein products of the fluidic resistances of the first and second channels and fluidic capacities of the respective first and second pumping chambers differ from products of the fluidic resistances of the third and fourth channels and fluidic capacities of the respective third and fourth pumping chambers, and wherein one of the first and second pumps has a low-pass characteristic and the other of the first and second pumps has a high-pass characteristic.
 12. A method for operating a microfluidic peristaltic pump having an inflow channel, a first pumping chamber operatively connected to the inflow channel by a first channel, and a second pumping chamber operatively connected to the inflow channel by a second channel, the method comprising: producing a throttling function of the first channel and the second channel, a fluidic resistance of the first channel being different from a fluidic resistance of the second channel; and deflecting a first membrane and a second membrane, respectively, in a time sequence when a pressure is applied in the inflow channel to produce a pumping function. 